Transcript Antiretroviral Therapy PPT Presentation

ANTIRETROVIRAL THERAPY
Dr. Samuel Mwaniki
(BPharm., MSc TID, UoN)
University of Nairobi
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Definition of ART
 Treatment with antiretroviral medicines,
against the retrovirus (HIV), which resides and
multiplies within the human body
 HIV; etiological agent of AIDS
 Hallmark of HIV; RNA virus that transcripts
DNA from RNA via the Reverse Transcriptase
enzyme
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Classification of
Antiretroviral medicines
 NRTI (Nucleoside Reverse Transcriptase Inhibitors)
 NtRTI (Nucleotide Reverse Transcriptase Inhibitors)
 NNRTI ( Non-Nucleoside Reverse Transcriptase
Inhibitors)
 PI (Protease Inhibitors)
 Entry Inhibitors
 Integrase Inhibitors
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NRTIs
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Abacavir (ABC)
Didanosine (DDI)
Emtricitabine (FTC)
Lamivudine (3TC)
Stavudine (D4T)
Zidovudine (AZT)
Tenofovir (TDF) - NtRTI
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NNRTIs
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Efavirenz (EFV)
Nevirapine (NVP)
Etravirine
Rilpivirine
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PIs
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Atazanavir (ATV)
Durunavir (DRV)
Fosamprenavir (f-APV)
Indinavir (IDV)
Lopinavir (LPV)
Nelfinavir (NFV)
Ritonavir (RTV)
Saquinavir (SQV)
Tripranvir (TPV)
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Other ARVs
Entry inhibitors: Enfuvirtide,
Maraviroc
Integrase inhibitors: Raltegravir,
Elvitegravir
Maturation inhibitors: Beviramat
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Uses of ART
ART (Antiretroviral Therapy)
PMTCT (Prevention of Mother To
Child Transmission)
PEP (Post Exposure Prophylaxis)
PrEP (Pre Exposure Prophylaxis)
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ART
 Combines at least 3 ARVs from at least 2
different classes.
 Why combination?
 Synergism
 Reduced toxicity
 Prevent resistance
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ART Combinations
2 NRTI + 1 NNRTI
1 NRTI + 1 NtRTI + 1 NNRTI
2NRTI + boosted PI
1 NRTI + 1 NtRTI + boosted PI
3 NRTI (One must be Abacavir)
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Goals of ART
 Maximal and durable suppression of viral replication
to prevent development of HIV, drug resistance and
treatment failure
 Restoration/ preservation of immunologic function
 Reduction of HIV-related morbidity and mortality
 Improvement of the patient’s quality of life
 Prevention of onward transmission of HIV infection
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Indications of ART
Indicated in all HIV-positive adults and adolescents with
the following:
 WHO clinical stage 1 or 2 and a CD4 count ≤ 350
cells/mm3,
 WHO clinical stage 3 or 4 regardless of CD4 count,
 HIV and TB co-infection regardless of the CD4 count,
 HIV/HBV co-infection with evidence of active liver
disease.
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First line ART regimens
Recommended first-line
antiretroviral regimens in treatment
of naive adults and adolescents are:
TDF + 3TC + EFV or NVP or
AZT + 3TC + NVP or EFV
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Changing to second line
 Treatment failure
 Clinical
 Immunological
 Virological
 Inability to tolerate a drug because of
adverse effects
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Second line ART
regimens
Recommended second-line for patients failing
first line therapy
First-line
Second-line
TDF + 3TC + EFV or NVP
AZT + 3TC + LPV/r or ATV/r
AZT + 3TC + EFV or NVP
TDF + 3TC + LPV/r or ATV/r
d4T + 3TC + EFV or NVP
TDF + 3TC + LPV/r or ATV/r
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MTCT
 MTCT accounts for more than 90% of pediatric HIV
infection.
 Risk factors for MTCT:
 Maternal (high viral load, advanced HIV disease, mixed
feeding )
 Obstetric (Vaginal delivery, prolonged rupture of
membranes >4 hours, placental infection)
 Infant (prematurity <37 weeks, low birth weight, oral
candidiasis)
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Interventions to reduce
MTCT
 Prevention of HIV Infection among all women of
reproductive age group from getting HIV
 Prevention of unintended pregnancies among HIVpositive women
 Effective interventions to reduce HIV transmission to
infants during pregnancy, labor, delivery and post.
 Chronic care and support for the HIV-infected
women, their infants, partners and families
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PMTCT ART regimens
 When to start:
 CD4 ≤350 cells/mm3 irrespective of clinical symptoms
OR
 WHO clinical stage 3 or 4 irrespective of CD4 cell count
 What to start:
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As adult/adolescent first-line
AZT preferred but TDF acceptable
EFV included as a NNRTI option (not in first trimester)
Infants: NVP, 3TC or AZT.
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PEP
Indications for PEP
 Occupational exposure (healthcare workers,
police)
 After RTA where there has been exposure to
other people’s blood
 Discordant couples following condom bursts
 Rape
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PEP regimens
 AZT/3TC: 1 bd for 28 days
 TDF/3TC: 1 od for 28 days
 Add Alluvia/ Kaletra: 2 bd for 28 days in case of high
risk
 Given at earliest possible opportunity, within 1-72
hours of exposure
 Use fixed dose combination to enhance adherence
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PrEP
 Studies carried out to evaluate efficacy
 iPrEx study– Preexposure Prophylaxis Initiative
 Multinational (Peru, Ecuador, South Africa, Brazil,
Thailand, United States)
 Effect of FTC/TDF compared with placebo on
reducing HIV acquisition among men and transgender
women who have sex with men
 Disproportionately affected by the epidemic
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Thank you
END
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